Interferons are macromolecules, presumably glycoproteins, which are synthesized in a variety of cells of vertebrates upon viral infection or some other stimuli. They are excreted, are bound to other cells and make these also inefficient in supporting the growth of a broad range of viruses. Interferon-mediated interference with viral replication has been reported to act at the level of translation and transcription. These seemingly divergent views of interferon action may be reconciled to a single mechanism by postulating that a cellular ribonuclease with proper specificity acts to reduce the intracellular accumulation of newly synthesized viral mRNA or to alter its capacity for translation. We propose to study (1) the modulation of such a ribonuclease by poly I:C and interferon and possible shifts in the location of the enzyme in relation to the sites of transcription and/or translation and (2) to investigate the effects of the ribonuclease on the accumulation and/or function of reovirus mRNAs and some kinds of cellular RNA (e.g. tRNA) critical for mRNA translation. The main, but not the only, systems to be examined are mouse L-929 cells and/or Ehrlich ascites tumor cells either infected with a double-stranded RNA virus, reovirus, and/or treated with poly I:C or mouse interferon. The features of these systems which make them suitable for this project include the following: reovirus replication in L-cells is interferon sensitive, an enzyme in the virion can transcribe both in vivo and in vitro the entire reo genome into ten messengers which can be separated from each other; these in turn are used as templates in the synthesis of double-stranded RNA; we developed in vivo and in vitro cell-free systems from L-cells in which viral messengers and viral double-stranded RNAs are transcribed and replicated and in which animal viral messengers can be translated.